Tuesday, June 03, 2008

A spliff test for science

It's the oldest but most important scientific question when two phenomena appear related: does one cause the other, vice versa, or is the apparent relationship pure coincidence? The question came up again this week when an Australian study demonstrated that 15 men who had all smoked marijuana heavily for at least 10 years had shrunken brain structures compared to those in non-users.

So was it the cannabis that on average shrank their hippocampuses by 12% and their amygdalas by 7%? Or were these same regions small to start with in these men, and if so, was it something that played a part in their strong liking for cannabis?

Certainly, both these regions are heavily affected by cannabis because they are both unusually rich in molecular receptors for delta-9-tetrahydrocannibol (THC), the psychoactive component in weed. The hippocampus is vital for storing memories and for the perception of time, and marijuana is known to affect both. Likewise, the amygdala is the brain's "fear" centre, and plays a key role in whether we react aggressively to events. Again, this fits with the observation that cannabis users sometimes develop paranoia.

To come back to the Australia study, is it equally possible that such prolonged exposure to cannabis wears out and shrinks these cannabis-sensitive regions? Again, we're back to cause and effect.

The only way to resolve it once and for all (as pointed out by the Australian researchers themselves at the end of their paper) would be to have brain scans of people before and after they began smoking cannabis. That way, you could see whether these regions did actually shrink the more cannabis they were exposed to. Or whether some people with unusually small regions at the outset turned out to be more attracted to the weed.

Unfortunately, a study to find out by deliberately giving cannabis to volunteers then following them for many years to see if their brains shrank would be unethical. Ethical comparisons could only be done if scans had been performed randomly on a wide population of children and kept as a general resource for researchers. If any of the scanned children subsequently became heavy dope users, it would be easy to check back and monitor whether brain regions were changing size. But obtaining the scans would cost a huge amount of money without any guarantee that it would yield any findings of interest.

So for now, we simply don't know for sure whether cannabis is genuinely changing brain architecture. And the same dilemmas apply to study of all addictions. Which is why some researchers contacted by New Scientist cautioned against sensationalising the Australian results.

"You must be very careful looking at this paper in isolation," says Tim Williams, who studies addiction at the University of Bristol. "With this kind of study, you can't tease out cause and effect." Williams also pointed out that a study in 2005 of long-term cannabis users by researchers at Harvard Medical School found that there was no effect on the size of their hippocampuses. "I'm surprised the Australians found an effect where others haven't," he adds.

The take-home message is clear! Be cautious about concluding too much from addiction studies which might confuse cause and effect. Yes, it could be down to the drug, but equally, it could be down to your pre-existing brain architecture, and the effect of that on your personality.

Do Australian cannabis smokers smoke more tobacco with their cannabis? ...and could this explain the variation from other countries studies? Given that nicotine has been identified as a destroying brain tissue it's possible.

The effects of THC on brain structure needs to be teased out - with all types of groups (cannabis eating only group, non tobacco cannabis smokers etc) - with before and afters. Yes, it's hard to create that.

...And an honest researcher would say that it's very hard to come to any conclusions without such a comprehensive study. So was this politicized science?

Did they control for alcohol use/abuse, other drugs, environmental factors, or genetics? If not, then this study is next to meaningless. The ridiculously small sample size doesn't help either, statistically speaking.

Even if it were true, what percentage of regular pot smokers smokes 5 joints a day for 10 years or more? If pot does affect the size of certain parts of the brain, do those effects disappear after usage stops? These are the things that a real study would have looked into.

I think this is an interesting theory and worth pursuing, but at the same time it might be a waste of time if it reveals what we already know about pot smoking.

I personally think it is down to the individual though. I have been smoking weed for about 9 years now. Not always heavily, but on average a joint a day. I haven't noticed a change in myself over that period of time and neither have my friends or family. I have a very good memory and don't tend to forget things.

"Grass makes u stupid...I've seen it with many of my friends. Slows reaction times, makes you forget."

I have friends who are stupid as a result of smoking and have no sense of time keeping but I also have friends who smoke a lot everyday and run their own businesses very successfully.

I do agree that possibly testing this theory on other mammals might produce some similar results to human tests.....

I'm pretty sure Australians do smoke much more tobacco with their pot than Americans (for example). I live in Sydney, and I think it'd actually be rare to find regular marijuana smokers in Australia who aren't also cigarette smokers. In fact I'd think five joints might even contain the tobacco of two cigarettes. At least one.

Also considering what the news has been like here recently I'd expect it to nearly certainly be politicized somehow.

This study appears more-and-more interesting. There is no suggested mechanisim to explain the brain shrinkage. However, it's possible that it's not specifically cannabis and it's active ingredient THC. But the correlation of brain shrinkage with use, could be explained specifically by the method of ingestion: ....smoking and associated carbon monoxide poisoning over time ...There's ample research indicating that carbon monoxide could explain the loss of mass of hipocampus. Try a search for the paper "Apoptosis and Delayed Neuronal Damage after Carbon Monoxide Poisoning in the Rat". Piantadosi et al, 1997. Also, "Dissociation Between Recall and Recognition Memory Performance in an Amnesic Patient with Hippocampal Damage Following Carbon Monoxide Poisoning", C. Bastin et al, 2004.

Cannabis smokers inhale very deeply and one would expect that said heavy smokers -per the study- would be subject to subclinical carbon monoxide poisoning. Over time cell shrinkage per these studies is within the real of possibility. If this hypothesis was correct (needs some research on CO levels in Cannabis smokers) then it may mean that the suggested health problem could be resolved by using non-smoking means of THC delivery - such as food rather than smoking.

Further, given the lack of associated research suggesting cannabis specifically causing hippocampus and amygdala shrinkage (in fact some research contradicts this), the CO hypothsesis seems more probable.

Some research shows that the role of tobacco smoking has been overlooked in alcohol brain damage research - "Quantitative Brain MRI in Alcohol Dependence: Preliminary Evidence for Effects of Concurrent Chronic Cigarette Smoking on Regional Brain Volumes." S. Gazdzinski et al, 2005.

So it would not be the first time that associated factors are overlooked, but with cannabis it's a more politicized environment.

Almost every day you read a report that Cannabis does this, or does that. Whilst I would be the last person to dismiss serious science, I cannot help feeling that most, if not all of these 'findings' are politically motivated (and therefore, potentially blatantly untrue).

I see far less such reports on alcohol use, but in this country alone, alcohol is responsible for 10,000 death a year, and Cannabis - none.

Of course, most, if not all politicians like a tipple, and Cannabis would be so hard to tax....